Cost-Effectiveness and Outcomes of Utilizing Tisagenlecleucel Therapy (CAR T-cell) in Pediatric Acute Lymphoblastic Leukemia in Comparison to Standard of Care (SoC) Therapies: A Scoping Review

Aims This review aims to assess the correlations between outcomes and cost of treatment methods for pediatric acute lymphoblastic leukemia patients, specifically comparing CAR T-cell therapy and Standard-of-Care (SoC) therapy. The socioeconomic background of patients will also be taken into consideration to see if there are differences in their outcomes. Methods Peer-reviewed publications were collected from PubMed and Web of Science. The keyword strings used were “acute lymphoblastic leukemia,” “pediatric acute lymphoblastic leukemia,” “pediatric,” “CAR T-cell therapy,” and “cost-effectiveness.” 27 citations were obtained. Titles were screened by 6 authors. Articles met the inclusion criteria including potential Quality-Adjusted Life Year (QALY) gains, mean price of CAR T-cell therapy and SoC therapy. The outcomes measured were presented in terms of total treatment cost for both CAR T-cell therapy and SoC treatments such as chemotherapy and/or hematopoietic stem-cell transplant. Results In the 6 comparative studies used, the overall cost and QALY of CAR T-cell therapy was higher than the SoC. In 4 of 6 studies, the price per QALY for CAR T-cell therapy was lower than the SoC treatment, ranging from $24,696 -$304,611 less per QALY. In the other 2 studies, the price per QALY for CAR T-cell therapy was higher by $6,452 and$18,874 per QALY. Conclusions Overall, CAR T-cell therapy was more expensive; however, it provided more QALY than other SoC’s. Future studies could determine if and how socioeconomic status, region, and race impact QALY for CAR T-cell, and how to mitigate barriers to access

Ocular hypotension, actin stress fiber disruption and phagocytosis increase by RKI-1447, a Rho-kinase inhibitor

Objective: The Rho GTPase/Rho kinase pathway is an important target in glaucoma treatment. This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor developed for cancer treatment, in a porcine ex vivo pigmentary glaucoma model. Materials and Methods: Twenty-eight fresh porcine anterior chambers were perfused with pigment medium (1.67×107 pigment particles/ml) for 48 hours before being subjected to the RKI-1447 (n=16) or the vehicle control (n=12). Another twelve eyes with normal medium perfusion served as the control. The intraocular pressure (IOP) was recorded at two-minute intervals and the outflow facility was calculated. To investigate the intracellular mechanism of the IOP reduction, primary trabecular meshwork cells were exposed to RKI-1447 or the vehicle control and then analyzed for changes in cytoskeleton, motility, and phagocytosis. Results: Compared to the baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P=0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14+/-2.59 mmHg to 13.38+/-0.91 mmHg (P=0.02). Pigment perfusion reduced the outflow facility from 0.27+/-0.03 at baseline to 0.18+/-0.02 at 48 hours (P<0.001). This was partially reversed with RKI-1447. RKI-1447 exhibited no apparent changes in the micro- or macroscopic appearance, including histology. Primary TM cells exposed to RKI-1447 showed a significant disruption of the actin cytoskeleton both in the presence and absence of pigment exposure (P<0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI reversed. Conclusions: RKI-1447 is a novel ROCK inhibitor that significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it especially useful for the treatment of secondary glaucomas with an increased phagocytosis load but also for other open angle glaucomas

Impact of Pigment Dispersion on Trabecular Meshwork Cells

Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 ± 0.3%, n=10, control (C): 38.4 ± 2.5%, n=11, P<0.001) and contraction at 24 hours onward (P<0.01). Phagocytosis declined (P: 68.7 ± 1.3%, C: 37.0 ± 1.1%, n=3, P<0.001) and migration was reduced after 6 hours (P: 28.0.1 ± 2.3, n=12, C: 40.6 ± 3.3, n=13, P<0.01). Microarray analysis revealed that Rho, IGF-1, and TGFβ signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigment glaucoma

Impact of Same-Session Trabectome Surgery on Ahmed Glaucoma Valve Outcomes

Purpose: To evaluate the efficacy and survival rates of same session ab interno trabeculectomy with the trabectome and Ahmed glaucoma valve implant (AT) in comparison to the Ahmed glaucoma valve alone (A). Method: A total of 107 eyes undergoing primary glaucoma surgery were enrolled in this retrospective comparative case series, including 48 eyes which underwent AT and 59 eyes which received A alone. Participants were identified using the procedural terminology codes, and their medical records were reviewed. The primary outcome measure was surgical success, defined as intraocular pressure (IOP) > 5 mmHg, ≤ 21 mmHg, and IOP reduction ≥ 20% from baseline at two consecutive visits after three months, no reoperation for glaucoma. Secondary outcome measures were IOP, the number of glaucoma medications, incidence of a hypertensive phase, and best corrected visual acuity (BCVA). Results: The cumulative probability of success at one year was 70% in AT, and 65% in A (p=0.85). IOP decreased significantly from 26.6 ± 10.1 mmHg at baseline to 14.7 ± 3.3 mmHg at the final follow-up in AT (p= 0.001). The corresponding numbers for A were 28.8 ± 10.2 and 16.7 ± 4.9, respectively (p= 0.001). The final IOP was significantly lower in AT (p= 0.022). The number of medications at baseline was comparable in both groups (2.6 ± 1.2 in AT and 2.5 ± 1.3 in A, p=0.851). Corresponding number at 1 year visit was 1.2±2 in AT and 2.8±1.8 in A (p=0.001). The incidence of a hypertensive phase was 18.7% in AT and 35.5% in A (p=0.05). HP resolved in only 30% of eyes. The criteria for HP resolution were fulfilled in 9 eyes (30%). There was no difference in the rate of resolution of the hypertensive phase between AT and A (33.3% and 28.5%, respectively, p=0.67). Conclusion: Ahmed glaucoma valve implant with same session trabectome surgery significantly decreased the rate of the hypertensive phase and postoperative IOP as well as the number of glaucoma medications

A participatory systems approach to design for safer integrated medicine management

It is recognised that whole systems approaches are required in the design and development of complex healthcare services. Application of a systems approach benefits from the involvement of key stakeholders. However, participation in the context of community based healthcare is particularly challenging due to busy and geographically distributed stakeholders. This study used action research to investigate what processes and methods were needed to successfully employ a participatory systems approach. Three participatory workshops planned and facilitated by method experts were held with 30 representative stakeholders. Various methods were used with them and evaluated through an audit of workshop outputs and a qualitative questionnaire. Findings on the method application and participation are presented and methodological challenges are discussed with reference to further research. Practitioner Summary: This study provides practical insights on how to apply a participatory systems approach to complex healthcare service design. Various template-based methods for systems thinking and risk-based thinking were efficiently and effectively applied with stakeholders

A participatory systems approach to design for safer integrated medicine management.

It is recognised that whole systems approaches are required in the design and development of complex health care services. Application of a systems approach benefits from the involvement of key stakeholders. However, participation in the context of community based health care is particularly challenging due to busy and geographically distributed stakeholders. This study used action research to investigate what processes and methods were needed to successfully employ a participatory systems approach. Three participatory workshops planned and facilitated by method experts were held with 30 representative stakeholders. Various methods were used with them and evaluated through an audit of workshop outputs and a qualitative questionnaire. Findings on the method application and participation are presented and methodological challenges are discussed with reference to further research. Practitioner Summary: This study provides practical insights on how to apply a participatory systems approach to complex health care service design. Various template-based methods for systems thinking and risk-based thinking were efficiently and effectively applied with stakeholders.This work was funded by NHS Islington Clinical Commissioning Group (CCG). Additional funding was provided by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research & Care (CLAHRC) East of England, at Cambridgeshire and Peterborough NHS Foundation Trust

Examining the provision of renal denervation therapy in low- and middle-income nations: Current landscape, challenges, future prospects—A mini perspective review

This paper delves into Renal Denervation Therapy as a promising intervention for resistant hypertension in low- and middle-income countries. With rates of hypertension increasing in LMICs due to lifestyle factors, RDN presents a potentially transformative approach. The methodology involves a comprehensive literature review, focusing on studies in LMICs that unveil proactive developments in standardized guidelines and precision targeting in clinical trials. LMICs actively contribute to research, emphasizing the safety and efficacy of RDN. However, despite these strides, the current landscape reveals challenges, encompassing initial costs, economic disparities, and limitations in healthcare infrastructure. Despite these hurdles, the paper envisions promising future prospects, emphasizing innovative strategies for cost-effective RDN implementation. It advocates for global collaboration and partnerships with international organizations, proposing the expansion of the Global SYMPLICITY Registry to include more LMICs; a testament to a commitment to research advancement. The paper concludes by highlighting comprehensive strategies to overcome challenges, making RDN financially viable in resource-limited settings. It underscores the potential for RDN to enhance global healthcare outcomes, particularly in regions grappling with diverse economic and healthcare challenges

A Case of Unilateral Presentation of Visual Snow Syndrome

Visual snow syndrome is an uncommon disease that is characterized by persistent positive phenomena that look like pixelated static similar to static on a television screen. Diagnostic criteria proposed by Schankin et al. define visual show as symptoms that persist for more than 3 months with at least two additional visual symptoms including, palinopsia, enhanced entopic phenomena, photophobia, or nyctalopia. These symptoms cannot be explained by typical migraine aura or another disorder. Onset may be sudden or gradual, but symptoms generally encompass the entire visual field in both eyes. Here, we present a unique case of visual snow syndrome that initially presents with unilateral symptoms